It is only three years since the first handful of cases of what would come to be known as acquired immune deficiency syndrome (AIDS) were described. Little is known about it -- how it's transmitted, if it's transmitted, who's at risk -- all are questions still under discussion.

For doctors on the front lines, "you knew what they had, and it was terrible," says Dr. Philip Berger, now chief of family and community medicine at St. Michael's Hospital in Toronto.

In 1984, Berger was one of the first doctors in Toronto treating patients with the new syndrome. He couldn't test for HIV -- it had just been established as the cause of the syndrome and there were no tests. He had no drugs to cure or even slow the disease. He couldn't advise on precautions, because it still wasn't completely clear how the disease was transmitted. Indeed, some researchers still argued it wasn't an infectious disease at all, but a result of over-use of party drugs such as amyl nitrate.

The armamentarium, Berger says, was terribly limited:

"You could be available, and you could be kind."

But that was it. During that early period of what has now become a pandemic, it seemed nothing could halt the inevitable. Patients with AIDS died, usually within a few years of diagnosis.

The prognosis depended on the initial diagnosis, according to Dr. John Bartlett, chief of infectious diseases at Johns Hopkins University. A patient with one of the more advanced opportunistic illnesses -- Pneumocystis carinii pneumonia, say, or Kaposi's sarcoma -- would have a year or so.

"If they had swollen glands, it might be the acute antiretroviral syndrome, and then they would live a bit longer," Bartlett says. "But they would die."

And there was essentially nothing to be done. "It was all temporizing," Bartlett says.

Contrast that with 2009.

So Much Change, So Quickly

Today, if a young homosexual man walks into a clinic with swollen glands, he'll first be tested for HIV, possibly with a rapid test that delivers results within a few hours or even -- with the latest technology -- in a few minutes.

If the cause of the swollen glands is indeed HIV, further tests will establish the viral load and -- to measure the impact the virus has had on the immune system -- the CD4-positive T cell count.

Once those things have been established, the medical team will start to devise a therapeutic regimen, choosing three of more of 25 drugs in five classes.

The virus that the young man harbors will be tested for resistance to the drugs, so that the best combination can be chosen. And drug interactions -- with other drugs he may be taking and among the HIV drugs themselves -- will also be accounted for.

Choosing a regimen is now such a complicated process that Berger's team includes a pharmacist who does a custom analysis of each patient to match him or her with the right drugs.

But perhaps the most striking contrast, according to Bartlett, is life expectancy.

That young man in 1984 could expect perhaps another decade at most, he said. After the advent of highly active antiretroviral therapy (HAART) in 1996, life expectancy shot up and today that same young man could expect to live another 50 years. (See HIV Life Expectancy Approaching Normal)

"That's amazing," Bartlett says. "You're going to have trouble finding another disease where there's been that kind of progress in that time span. It is clearly the best success story in medicine since H. influenzae vaccine or even eradication of smallpox."

Mark W. Kline, MD, of Baylor College of Medicine and Texas Children's Hospital in Houston has a 17-year-old patient who was one of the first children given HAART therapy in 1996. She'd been diagnosed with HIV when an infant. "Her adoptive parents were told not to expect her to survive to school age," he said in an e-mail. "Today, she's a high school varsity cheerleader."

The next challenge, Bartlett says, is to find a cure.

That seems likely to be a serious hurdle, and no one is predicting it will be cleared any time soon. When it comes to HIV/AIDS, optimism has repeatedly foundered on the hard rock of reality.

Finding the Cause, Slowing the Progress

It's worth noting that 25 years ago researchers were just starting to pin down the pathogen that would become known as HIV. In labs in Paris and Bethesda, Dr. Luc Montagnier and Dr. Robert Gallo were identifying the virus and showing that it caused AIDS.

The findings generated immense optimism.

In 1984, then Health and Human Services Secretary Margaret Heckler said Gallo's work would soon lead to a commercially available test. And, she added, "We hope to have a vaccine ready for testing in about two years."

That prediction was woefully off-base. It was only this year that researchers finally found a vaccine against HIV that had any effect whatsoever -- about a 30 percent benefit.

Heckler concluded in that speech that "yet another terrible disease is about to yield to patience, persistence, and outright genius."

Wrong again. HIV/AIDS remains terrible, although no longer an outright death sentence for those lucky enough to live in the developed world.

But it has not yet yielded, despite all the patience, persistence, and outright genius in the world at large.

That said, a major turning point came in 1996, when researchers showed that a combination of three antiretroviral drugs -- attacking the virus from different angles -- could slow or stop viral replication and restore immune function.

Today, says Dr. Joel Gallant, director of Johns Hopkins' Moore Clinic for HIV Care, if our hypothetical young man walked in "I would assure him that he will not die of AIDS if he remains under medical care by an HIV expert and takes his medications as prescribed."

"Overnight," Bartlett says, his AIDS clinic at Hopkins "became a clinic where people were going to live. It was pretty amazing."

It seemed possible, even, that the virus might be eradicated by such an approach, but that, too, turned out to be an overoptimistic mirage. HIV was too wily and had too many hiding places.

Attention turned to making more and better drugs, reducing side effects, and finding ways to overcome or prevent resistance. And by any measure, those efforts have paid off.

Today, a Tale of Two Worlds

In the developed world, patients on many current regimens need take only a single pill once a day, a far cry from the late 1990s, when the rule was several dozen, taken at various times, with and without food depending on the drug.

Adverse effects still occur but they are more easily managed.

And resistance is constantly monitored, so that medications can be switched if it develops. And there are many more drugs, so that switching is possible.

There has been, Toronto's Berger says, "a massive transformation of the whole terrain of HIV. I wouldn't have believed it 20 years ago."

But the developed world is only a part of the story. In many parts of the world, access to the life-saving drugs remains poor and HIV/AIDS remains a death sentence.

Berger spends part of his time working in Lesotho, one of the hardest-hit regions of Africa. In that country five years ago, he said, it was like 1984 in Canada.

"People were dying in front of your eyes," he says.

Matters have improved -- at least a little -- as the world finally starts to get together on battling the pandemic. In Lesotho, he says, some of the advances -- HIV testing and CD4 counts, for instance -- are now available most of the time and others occasionally.

And overall, the most recent U.N. AIDS report offers grounds for modest optimism that efforts to slow the pandemic are having an effect.

Chief among those efforts, according to Bartlett of Johns Hopkins, is the President's Emergency Plan for AIDS Relief, or PEPFAR, which has poured money into treatment and prevention in the developing world.

Despite some controversy when it started, the program is now seen as a major success story that "dwarfs" any other health program in our lifetimes, he says.